Leishmanicidal and healing effects of 3ß,6ß,16ß-trihydroxy lup-20 (29)-ene isolated from Combretum leprosum on Leishmania braziliensis infection in vitro and in vivo.

Treatment of cutaneous leishmaniasis depends on drugs that potentially cause serious side effects and resistance. Thus, topical therapies are attractive alternatives to the drugs currently used. 3ß, 6ß, 16ß-trihydroxylup-20 (29)-ene is a lupane triterpene isolated from Combretum leprosum Mart. leaves (CLF-1), with reports of in vitro antileishmanial effect against L. amazonensis and to promote lesion healing in animal model. Herein, we evaluated the in vitro and in vivo antileishmanial and healing effects of CLF-1 against L. braziliensis. CLF-1 treatment showed low toxicity in macrophages and significantly reduced parasite load in vitro. CLF-1 induced higher IL-12 and TNF-α production and more discrete IL-4 and IL-10 production. For in vivo evaluation, a CLF-1 cream formulation was prepared to treat hamsters infected with L. braziliensis. CLF-1 treatment was able to reduce parasite load of the infected skin and lymph node more efficiently than the conventional treatment. Histopathological analysis indicated a strong inflammatory response accompanied by an important healing response. Data from this study indicate that topical CLF-1 treatment was effective and non-toxic in L. braziliensis infected hamsters suggesting its potential for further development as a future therapeutic intervention.

Cashew apple pectin as a carrier matrix for mangiferin: Physicochemical characterization, in vitro release and biological evaluation in human neutrophils.

In this work, cashew apple pectin (CP) of the species Anacardium occidentale L. was used as an encapsulation matrix for hydrophobic drugs. The model drug chosen was mangiferin (Mf), a glycosylated C-xanthone which has antioxidant properties but low solubility in aqueous medium. CP (1-100 µg mL-1) was not toxic to human neutrophils and also did not significantly interfere with the pro-inflammatory mechanism of these cells in the concentration range of 12.5 and 100 µg mL-1. The results are promising because they show that pectin encapsulated mangiferin after spray drying presented an efficiency of 82.02%. The results obtained in the dissolution test, simulating the release of mangiferin in the gastrointestinal tract (pH 1.2, 4.6 and 6.8) and using Franz diffusion cells (pH 7.4), showed that cashew pectin may be a promising vehicle in prolonged drug delivery systems for both oral and dermal applications.

Triplaris gardneriana seeds extract exhibits in vitro anti-inflammatory properties in human neutrophils after oxidative treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Triplaris gardneriana Wedd. (Polygonaceae family) is a plant species from Brazilian semiarid region which is used in local traditional medicine for the treatment of inflammatory conditions such as hemorrhoids. AIM OF THE STUDY: In this study, the in vitro anti-inflammatory activity of different concentrations of ethanolic extract from T. gardneriana seeds (EETg) was performed in order to contribute to the knowledge about etnomedicinal use of this plant species. MATERIALS AND METHODS: The anti-inflammatory properties were evaluated through different approaches, such as in vitro protein anti-denaturation test, scavenging of reactive oxygen species (ROS) and myeloperoxidase (MPO) inhibition in human neutrophils activated by phorbol-12-myristate-13-acetate (PMA). Besides that, molecular docking was performed to provide new insights about the interaction between the major phenolic components in the plant extract and MPO. RESULTS: EETg was characterized showing a total phenol content of 153.5 ± 6.3 µg gallic acid equivalent/mg extract, ability to remove hydrogen peroxide (H2O2) in a concentration-dependent manner and had a spectroscopic profile which suggests the presence of hydroxyl groups. EETg was able to prevent protein denaturation ranging from 40.17 to 75.09%. The extract, at 10 and 20 µg/mL, was able to modulate neutrophils pro-inflammatory functions, such as degranulation and burst respiratory. In both assays, the EETg had anti-inflammatory effect comparable to nonsteroidal anti-inflammatory drugs. Among the main phenolic compounds of EETg, quercitrin, quercetin and catechin showed the highest binding affinity in silico to MPO. CONCLUSION: This study demonstrated, for the first time, that the anti-inflammatory effect of T. gardneriana seeds occurs due to its modulatory effect on human neutrophil degranulation and free-radical scavenging activity.

Vitamin D (VD3) antioxidative and anti-inflammatory activities: Peripheral and central effects.

Vitamin D (VD3, cholecalciferol), besides its role on bone calcium homeostasis, has also been shown to present anti-inflammatory actions. The objectives of the present work were to further extend these findings, focusing onVD3action mechanisms at the molecular level and onits central and peripheral effects. For that, VD3 antinociceptive and mainly anti-inflammatory activities were evaluated by acute models of nociception (formalin test) and inflammation (carrageenan-induced paw edema), in mice pretreated orally for 7 days with VD3 (0.5 and 1.0 mg/kg). Afterwards, the edematous paws were evaluated by immunohistochemical assays for TNF-alpha. In addition, brains from mice pretreated with VD3, at the same conditions, were harvested for iNOS andCOX-2 immunohistochemical (IHC) assays. The anti-inflammatory effect of VD3 on human neutrophil degranulation was evaluated by the release of myeloperoxidase (MPO) activity, as well as by the reactive oxygen species production. VD3 significantly reduced the licking time in the formalin test, at the second phase (inflammatory pain). VD3 also reduced the edema volume and the number of polymorphonuclear (PMN) cells, as well as the TNF-alpha expression in the edematous paws, compared with the control group. Furthermore, VD3 significantly decreased iNOS and COX-2 expressions in brain areas, such as hippocampus and prefrontal cortex, and inhibited the degranulation of activated neutrophils by the reduction of ROS production and MPO release. Based in these results, VD3 presents anti-inflammatory and antioxidative effects, manifested at peripheral and central sites as showed in the present work for the first time.